Nanosecond pulsed electric fields (nsPEF) applied to tissue have been shown to impart low energy in the tissue leading to very little heat production. The ability of nsPEF to penetrate into the cell to permeabilize intracellular organelles is known. (See Schoenbach et al., 2001, Bioelectromagnetics 22, 440-448; Buescher and Schoenbach, 2003, IEEE Transactions on Dielectrics and Electrical Insulation 10, 788-794). During the past two years a group including some of the present Inventors have treated over 400 murine melanomas in 220 mice with nsPEF comprising 40 kV/cm electric field pulses 300 nanoseconds in duration with dramatic results (See Nuccitelli et al., 2006, Biochem. Biophys. Res. Commun. 343, 351-360). Every tumor exposed to 300 such pulses exhibited rapid pyknosis and, reduced blood flow and shrinks by an average of 90% within two weeks. A second treatment of 300 pulses was shown to completely eliminate the melanoma without recurrence. This very short total field exposure time of only 18011S stimulates melanomas to self-destruct without drugs or significant side effects.
The nsPEFs differ from those commonly used for classical electroporation in at least three (3) ways. First, they typically have a 100-fold faster rise time such as <50 nsec. Second, the typically have 1000-fold shorter duration such as about 300 nsec. Thirdly, nsPEFs typically provide 20-fold larger amplitude such as around 15 kV. These differences in pulse parameters are believed to allow nanosecond width pulses to penetrate into cells and electroporate organelle membranes in addition to the plasma membrane. Two separate mechanisms are believed to lead the intracellular penetration: 1) The rise time of the nsPEFs is faster than the charging time of the plasma membrane, resulting in penetration of the electric field into the cell interior. This internal field will generate a current that charges the outer plasma membrane. Most cells exhibit a charging time constant of about 100 ps so they will be about 95% charged at 300 ns. After this charging time, the resulting charge redistribution will screen out the electric field from the cell interior unless the field strength within the plasma membrane has become large enough to generate pores that provide the second mechanism for intracellular penetration: 2) If the potential difference across the membrane exceeds about 1.6 volts, the formation of nanopores occurs within tens of nanoseconds. This allows conduction current to enter the cell during the time that the pores are open. For the large field strengths that we use, all of the molecules and organelles inside the cell will be exposed to the imposed electric field for up to hundreds of nanoseconds during each pulse due to the timing of the charging current and the open time of the field-induced pores. By applying multiple pulses, the total time of field exposure can be increased in proportion to the number of pulses applied.
Work to date studying the effects of nsPEF on skin tumors has been conducted on mice using either parallel plate electrodes or needle electrodes to apply the electric fields to the skin. However, mice skin is much thinner as compared to human skin and the skin of other mammals. Accordingly, a new device is needed that is adapted for treating thicker, human and other mammalian skin with electrotherapy for benign and malignant cysts, growths, polyps or tumors on or within internal body organs.